Evaluating the Baylis-Hillman reaction of cyclic enones using surfactants in water

Conjugated cyclic enones react smoothly in water with a variety of aldehydes (Baylis-Hillman reaction) in the presence of surfactants above their critical micelle concentrations (CMC).

Direct access to functionalized cyclic enones using Mannich, Morita-Baylis-Hillman and elimination reactions

A series of highly functionalized cyclic enones were obtained from Mannich, Morita-Baylis-Hiliman and elimination reaction with cyclic enones.

Cinchona alkaloids and BINOL derivatives as privileged catalysts or ligands in asymmetric synthesis

During the last fifteen years organocatalysis emerged as a powerful tool for the enantioselective functionalization of the most different organic molecules. Both C-C and C-heteroatom bonds can be formed in an enantioselective fashion using many types of catalyst and the field is always growing. Many kind of chiral catalysts have emerged as privileged, but among them Proline, cinchona alkaloids, BINOL, and their derivatives showed to be particularly useful chiral scaffolds. This thesis, after a short presentation of many organocatalysts and activation modes, focuses mainly on cinchona alkaloid derived primary amines and BINOL derived chiral Brønsted acids, describing their properties and applications. Then, in the experimental part, these compounds are used for the catalysis of new transformations. The enantioselective Friedel-Crafts alkylation of cyclic enones with naphthols using cinchona alkaloid derived primary amines as catalysts is presented and discussed. The results of this work were very good and this resulted also in a publication. The same catalysts are then used to accomplish the enantioselective addition of indoles to cyclic enones. Many catalysts in combination with many acids as co-catalysts were tried and the reaction was fully studied. Selective N-alkylation was obtained in many cases, in combination with quite good to good enantioselectivities. Also other kind of catalysis were tried for this reaction, with interesting results. Another aza-Michael reaction between OH-free hydroxylamines and nitrostyrene using cinchona alkaloid derived thioureas is briefly discussed. Then our attention focused on Brønsted acid catalyzed transformations. With this regard, the Prins cyclization, a reaction never accomplished in an enantioselective fashion until now, is presented and developed. The results obtained are promising. In the last part of this thesis the work carried out abroad is presented. In Prof. Rueping laboratories, an enantioselective Nazarov cyclization using cooperative catalysis and the enantioselective desymmetrization of meso-hydrobenzoin catalyzed by Brønsted acid were studied.

Expedient construction of the vibsanin E core without the use of protecting groups

The tricyclic core of vibsanin E was constructed without the use of a protecting group in six steps. The El Gaied Baylis-Hillman variant was key to allowing the Bronsted acid induced tandem cyclization forming rings B and C in one operation.

Towards the total synthesis of vibsanin E, 15-O-methylcyclovibsanin B, 3-hydroxyvibsanin E, furanovibsanin A, and 3-O-methylfuranovibsanin A

Studies detailing synthetic approaches to a variety of biosynthetically related vibsanin-type diterpenes (i.e. vibsanin E, 15-O-methylcyclovibsanin B, 3-hydroxy-vibsanin E, furano-vibsanin A, and 3-O-methylfuranovibsanin A) are discussed. Biogenetically modelled approaches are coupled with an in-vestigation of classical and modern six- to seven-membered ring-expansion protocols, which gain access to the central core of these natural products. (c) Wiley-VCH Verlag GmbH & Co.

Cyclic strain disrupts endothelial network formation on Matrigel

Most forms of tissue healing depend critically on revascularisation. In soft tissues and in vitro, mechanical stimuli have been shown to promote vessel-forming activity. However, in bone defects, increased interfragmentary motion impairs vascular regeneration. Because these effects seem contradictory, we aimed to determine whether a range of mechanical stimuli exists in which angiogenesis is favoured. A series of cyclic strain magnitudes were applied to a Matrigel-based “tube formation” assay and the total lengths of networks formed by human microvascular endothelial cells measured at 24 h. Network lengths were reduced at all strain levels, compared to unstretched controls. However, the levels of pro-angiogenic matrix metalloproteases-2 and -9 in the corresponding conditioned media were unchanged by strain, and vascular endothelial growth factor was uniformly elevated in stretched conditions. By repeating the assay with the addition of conditioned media from mesenchymal stem cells cultivated in similar conditions, paracrine stimuli were shown to increase network lengths, but not to alter the negative effect of cyclic stretching. Together, these results demonstrate that directly applied periodic strains can inhibit endothelial organisation in vitro, and suggest that this may be due to physical disruption rather than biochemical modulation. Most importantly, the results indicate that the straining of endothelial cells and their assembly into vascular-like structures must be studied simultaneously to adequately characterise the mechanical influence on vessel formation.

Experimental and theoretical studies of the redox potentials of cyclic nitroxides

The redox potentials of 25 cyclic nitroxides from four different structural classes (pyrrolidine, piperidine, isoindoline, and azaphenalene) were determined experimentally by cyclic voltammetry in acetonitrile, and also via high-level ab initio molecular orbital calculations. It is shown that the potentials are influenced by the type of ring system, ring substituents and/or groups surrounding the radical moiety. For the pyrrolidine, piperidine, and isoindolines there is excellent agreement (mean absolute deviation of 0.05 V) between the calculated and experimental oxidation potentials; for the azaphenalenes, however, there is an extraordinary discrepancy (mean absolute deviation of 0.60 V), implying that their one-electron oxidation might involve additional processes not considered in the theoretical calculations. This recently developed azaphenalene class of nitroxide represents a new variant of a nitroxide ring fused to an aromatic system and details of the synthesis of five derivatives involving differing aryl substitution are also presented.

Accelerated computation of cyclic steady state for simulated-moving-bed processes

Industrial applications of the simulated-moving-bed (SMB) chromatographic technology have brought an emergent demand to improve the SMB process operation for higher efficiency and better robustness. Improved process modelling and more-efficient model computation will pave a path to meet this demand. However, the SMB unit operation exhibits complex dynamics, leading to challenges in SMB process modelling and model computation. One of the significant problems is how to quickly obtain the steady state of an SMB process model, as process metrics at the steady state are critical for process design and real-time control. The conventional computation method, which solves the process model cycle by cycle and takes the solution only when a cyclic steady state is reached after a certain number of switching, is computationally expensive. Adopting the concept of quasi-envelope (QE), this work treats the SMB operation as a pseudo-oscillatory process because of its large number of continuous switching. Then, an innovative QE computation scheme is developed to quickly obtain the steady state solution of an SMB model for any arbitrary initial condition. The QE computation scheme allows larger steps to be taken for predicting the slow change of the starting state within each switching. Incorporating with the wavelet-based technique, this scheme is demonstrated to be effective and efficient for an SMB sugar separation process. Moreover, investigations are also carried out on when the computation scheme should be activated and how the convergence of the scheme is affected by a variable stepsize.

A cyclic porphyrin tetramer linked by azo and butadiyne bridges

A soluble cyclic porphyrin oligomer (CPO) consisting of four 5,10- diarylporphyrins linked by alternating azo and butadiyne bridges has been synthesised via an aminated dinickel(II) butadiyne dimer. This is the first cyclic tetramer that combines both azo and butadiyne bridges and extends the azoporphyrin family, which comprises only a very few examples. The electronic absorption spectrum of the tetramer is more similar to spectra of azoporphyrins than to those of butadiyne-linked dimers or tetramer, exhibiting a two component Soret band with a splitting of 4190 cm-1 and a strongly red-shifted Q band maximum at 735 nm.

Extracellular matrix of the human cyclic corpus luteum

Extracellular matrix regulates many cellular processes likely to be important for development and regression of corpora lutea. Therefore, we identified the types and components of the extracellular matrix of the human corpus luteum at different stages of the menstrual cycle. Two different types of extracellular matrix were identified by electron microscopy; subendothelial basal laminas and an interstitial matrix located as aggregates at irregular intervals between the non-vascular cells. No basal laminas were associated with luteal cells. At all stages, collagen type IV α1 and laminins α5, β2 and γ1 were localized by immunohistochemistry to subendothelial basal laminas, and collagen type IV α1 and laminins α2, α5, β1 and β2 localized in the interstitial matrix. Laminin α4 and β1 chains occurred in the subendothelial basal lamina from mid-luteal stage to regression; at earlier stages, a punctate pattern of staining was observed. Therefore, human luteal subendothelial basal laminas potentially contain laminin 11 during early luteal development and, additionally, laminins 8, 9 and 10 at the mid-luteal phase. Laminin α1 and α3 chains were not detected in corpora lutea. Versican localized to the connective tissue extremities of the corpus luteum. Thus, during the formation of the human corpus luteum, remodelling of extracellular matrix does not result in basal laminas as present in the adrenal cortex or ovarian follicle. Instead, novel aggregates of interstitial matrix of collagen and laminin are deposited within the luteal parenchyma, and it remains to be seen whether this matrix is important for maintaining the luteal cell phenotype.